The poisonous brown recluse spider (Loxosceles reclusa) may cause extensive necrotic lesions in human skin by bites which deposit 5 to 25 microliters of venom into the skin. These wounds are the result of a dermonecrotoxin contained in the venom which has been identified in discrete portions of plyacrylamide gels and Sephadex column eluants. Clarification of the exact mechanism by which this toxin functions has been handicapped by the absence of any in vitro assay for the toxin and the need to rely on whole animal studies. Our recent discovery that fat cells purified from the rat foot pad are lysed by venom suggests these cells will provide a convenient target tissue for the dermotoxic principle. It will be important to evaluate the relationship of the venom hemolysin, dermotoxin and fat cell lysin. A second activity of venom under investigation is the chemotaxigenic factor which acts on guinea pig complement to release chemotaxins which activate guinea pig peritoneal exudate cells. Venom alone is not leukotactic but is so in the presence of fresh serum. Whether the active molecules in fresh sera arise from C3, C5 or other complement components is under investigaton.